Acetic Anhydride → HCID 11845599, compound

HRID 2216590Notes

Reaction equation

HRID 2216590 reaction equation
[O:1]=[S:2]1(=[O:13])[CH2:7][CH2:6][N:5]2[N:8]=[C:9]([CH:11]=[O:12])[CH:10]=[C:4]2[CH2:3]1.[Mg+2].[Br-].[Br-].[N+:17]([C:20]1[CH:38]=[CH:37][C:23]([CH2:24][O:25][C:26]([C:28]2[N:29]3[C@H:32]([S:33][CH:34]=2)[C@@H:31]([Br:35])[C:30]3=[O:36])=[O:27])=[CH:22][CH:21]=1)([O-:19])=[O:18].[C:39](OC(=O)C)(=[O:41])[CH3:40]>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.CCN(CC)CC.C1COCC1.C(#N)C>[N+:17]([C:20]1[CH:38]=[CH:37][C:23]([CH2:24][O:25][C:26]([C:28]2[N:29]3[C@H:32]([S:33][CH:34]=2)[C:31]([CH:11]([O:12][C:39](=[O:41])[CH3:40])[C:9]2[CH:10]=[C:4]4[CH2:3][S:2](=[O:1])(=[O:13])[CH2:7][CH2:6][N:5]4[N:8]=2)([Br:35])[C:30]3=[O:36])=[O:27])=[CH:22][CH:21]=1)([O-:19])=[O:18]

Participants

10

Reactant 4

HCID 7918Acetic Anhydride2×HCID 82241Magnesium BromideHCID 11280588(5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl esterHCID 210576875,5-Dioxo-4,5,6,7-tetrahydro-5lambda~6~-pyrazolo[5,1-c][1,4]thiazine-2-carbaldehyde

Product 1

HCID 11845599HCID 11845599, compoundYield 22%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

5,5-Dioxo-4,5,6,7-tetrahydro-5λ6-pyrazolo[5,1-c][1,4]thiazine-2-carbaldehyde (1.95 g) was added to the dry acetonitrile (112 mL) solution of anhydrous MgBr2 (cont. 98%) (5.48 g) under a nitrogen atmosphere at room temperature. The dry THF solution (112 mL) of (5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl ester (cont. 96.5%) (3.88 g) was added to the mixture, cooled to −20° C., and Et3N (cont. 99%) (3.79 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 3 h at −20° C. and treated with acetic anhydride (cont. 97%) (3.79 mL) and DMAP (cont. 99%) (120 mg) in one portion. The reaction mixture was warmed to 0° C. and stirred for 16 h at 0° C. To the reaction mixture was added acetic anhydride (cont. 97%) (0.95 mL) and DMAP (cont. 99%) (120 mg) in one portion. The mixture was diluted with ethyl acetate and washed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate and brine. The organic layer was dried (MgSO4), followed by concentration under reduced pressure. The residue was purified with a silica-gel column chromatography (CHCl3:acetone=19:1–4:1) to give the titled compound as a pale brown amorphous solid (diastereo-mixture (8:2), 1.35 g, 22%).

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 16 h at 0° C
  3. washwashed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationfollowed by concentration under reduced pressure
  6. customThe residue was purified with a silica-gel column chromatography (CHCl3:acetone=19:1–4:1)

Sources & evidence

ORD record
ord-edc6cabd2cd84b0ebae033b141b633f3
Source dataset
uspto-grants-2006_09
Patent number
US07112582B2

Reaction notes

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